Evidence map›Paper›PMID 38243838›Full record

ArticleThe Journal of infectious diseases2024

Loratadine as an Anti-inflammatory Agent Against Clostridium difficile Toxin B.

Ying Xie, Sophie Irwin, Andrea Chupina Estrada, Becca Nelson, Ashlen Bullock, Lindsey Fontenot, Hanping Feng, Mingjun Sun, Hon Wai Koon

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
2.3field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Ying XieVatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.ORCID 0000-0003-0620-1519
Sophie IrwinVatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.ORCID 0000-0002-2821-8015
Andrea Chupina EstradaVatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.ORCID 0000-0002-3331-0959
Becca NelsonVatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.ORCID 0000-0001-7338-3215
Ashlen BullockVatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.ORCID 0000-0002-6258-7420
Lindsey FontenotVatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.ORCID 0000-0002-7430-5275
Hanping FengDepartment of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, Maryland, USA.ORCID 0000-0002-8685-1812
Mingjun SunDepartment of Gastroenterology, The First Hospital of China Medical University, Shenyang City, China.ORCID 0000-0001-8748-4658
Hon Wai KoonVatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.ORCID 0000-0003-0618-0869
University of California, Los Angeles · USFirst Hospital of China Medical University · CNUniversity of Maryland, Baltimore · US

Funding

Oral elafin formulation for intestinal fibrosisR01DK128142 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOON, HON WAI · 2022 to 2025
$1.4M
Orally active metabolite therapy against C. difficile infectionR21AI137663 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOON, HON WAI · 2019 to 2020
$429k
CCF 623027China Scholarship Council 202008210019NIAID NIH HHS R21 AI137663NIDDK NIH HHS R01 DK128142NIH HHS R01-DK128142
6 · The paper itself

Abstract

backgroundClostridium difficile infection (CDI) is a debilitating nosocomial infection. C. difficile produces toxins A and B, which cause inflammation. Existing therapies have issues with recurrence, cost, and safety. We aim to discover a safe, effective, and economical nonmicrobiological therapeutic approach against CDI.

methodsWe included human primary peripheral blood mononuclear cells (PBMCs), fresh human colonic explants, and humanized HuCD34-NCG mice. Toxin A+B+ VPI 10463 and A-B+ ribotype 017 C. difficile strains were used. We used single-cell RNA profiling and high-throughput screening to find actionable toxin B-dependent pathways in PBMCs.

resultsHistamine 1 receptor-related drugs were found among the hit compounds that reversed toxin-mediated macrophage inflammatory protein (MIP) 1α expression in PBMCs. We identified loratadine as the safest representative antihistamine for therapeutic development. Loratadine inhibited toxin B-induced MIP-1α secretion in fresh human colonic tissues. Oral loratadine (10 mg/kg/d) maintained survival, inhibited intestinal CCl3 messenger RNA expression, and prevented vancomycin-associated recurrence in the VPI 10463-infected mice and ribotype 017-infected hamsters. Splenocytes from loratadine-treated mice conferred anti-inflammatory effects to the VPI 10463-infected T/B-cell--deficient Rag-/- mice. Oral loratadine suppressed human MIP-1α expression in monocytes/macrophages in toxin B-expressing ribotype 017-infected humanized HuCD34-NCG mice.

conclusionsLoratadine may be repurposed to optimize existing therapies against CDI.

Indexed as

Anti-Inflammatory AgentsBacterial ProteinsBacterial ToxinsClostridioides difficileLeukocytes, MononuclearLoratadineAnimalsChemokine CCL3Clostridium InfectionsColonEnterotoxinsHumansMiceAnti-Inflammatory AgentsBacterial ProteinsBacterial ToxinsChemokine CCL3EnterotoxinsLoratadinetoxB protein, Clostridium difficilecytokinehistamine receptorsplenocytes

Identifiers

PMID38243838
PMCPMC11420802
OpenAlexW4391055823

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.